Thursday, February 5, 2015

Obinutuzumab in CLL (chronic lymphocytic leukemia): Rituximab with an Attitude

This second  OncLive video with Drs. Byrd, Furman, Kipps, and Ma was actually the first, the lead-in to my prior post. In fact the last few minutes of this video are the first few minutes of the video with the same doctors seen on my the recent post discussing ibrutinib.

Obinutuzumab is a powerful antibody directed against CD20 as is rituximab and ofatumumab but it seems to promise better responses as part of a therapeutic combination at least in some circumstances In this case when used with chlorambucil (a gentle form of chemotherapy or alkylating agent similar to cyclophosphamide, the C in FCR), it clearly delivered significantly deeper and longer responses than the other arms of the trial.

While the video session is clearly aimed at the oncology doctors, and our eyes may glaze over when there is a detailed discussion concerning the choice of the best steroid to use to abrogate the potential severe infusion reactions associated with this potent antibody, it is worthwhile to listen and catch the data on obinutuzumab.

It is nice to listen the experts for once discussing the real world concerns about cost and insurance.

It is also good to hear Dr. Kipps point out the critical role of the infusion nurses in keeping us well and safe.

Here is the results from the abstract published in the NEJM with Valentin Goede as the lead author. It is a study that randomized patients to one of three possible therapies: chlorambucil alone, or combined with either rituximab or with obinutuzumab. The trial patients were all untreated and would generally be considered to be too sick due to renal disease or other problems to risk more robust chemo-immunotherapy such as FCR.

Here is part of abstract results:

Obinutuzumab plus Chlorambucil in
Patients with CLL and Coexisting Conditions 


The patients had a median age of 73 years, creatinine clearance of 62 ml per minute, and CIRS score of 8 at baseline. Treatment with obinutuzumab–chlorambucil or rituximab–chlorambucil, as compared with chlorambucil monotherapy, increased response rates and prolonged progression-free survival (median progression-free survival, 26.7 months with obinutuzumab–chlorambucil vs. 11.1 months with chlorambucil alone;... and 16.3 months with rituximab–chlorambucil vs. 11.1 months with chlorambucil alone;

Please note that the impressive 10 month improvement in the mean progression free survival noted with obinutuzumab–chlorambucil compared to rituximab- chlorambucil. Comparison to chlorambucil monotherapy is not helpful as it is rarely used this way in the USA because of its known lack of efficacy.

CIRS score is a marker of the degree of co-existing illness.

It is important to remember that a benefit demonstrated with one combination is no guarantee that the antibody would demonstrate a similar benefit in any other combos. Assumptions can be dangerous in cancer care.

I am waiting for the published data that Dr. Kipps that show the results of the combination bendamustine and obinutuzumab.

Lastly, what we all really want (if we can't get a cure) is a durable remission. The mean progression free survival was a little over two years (26.7 months) for the mostly elderly treatment naive patients.

Is that enough for you?  Two years is nice respite, especially for a pretty gentle therapy used in a delicate population, but I wanted a longer time before half the group had to live with the reality of their cancer progressing again.

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